Fiber-specific white matter alterations in early-stage tremor-dominant Parkinson's disease.
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ABSTRACT:
SUBMITTER: Andica C
PROVIDER: S-EPMC8233424 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionDiffusion magnetic resonance imaging may allow for microscopic characterization of white matter degeneration in early stages of Alzheimer's disease.MethodsMultishell Diffusion magnetic resonance imaging data were acquired from 100 participants (40 cognitively normal, 38 with subjective cognitive decline, and 22 with mild cognitive impairment [MCI]). White matter microscopic degeneration in 27 major tracts of interest was assessed using diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging, and q-space imaging.ResultsLower DTI fractional anisotropy and higher radial diffusivity were observed in the cingulum, thalamic radiation, and forceps major of participants with MCI. These tracts of interest also had the highest predictive power to discriminate groups. Diffusion metrics were associated with cognitive performance, particularly Rey Auditory Verbal Learning Test immediate recall, with the highest association observed in participants with MCI.DiscussionWhile DTI was the most sensitive, neurite orientation dispersion and density imaging and q-space imaging complementarily characterized reduced axonal density accompanied with dispersed and less restricted white matter microstructures.
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Project description:Huntington's disease (HD) is a monogenic, fully penetrant neurodegenerative disorder. Widespread white matter damage affects the brain of patients with HD at very early stages of the disease. Fixel-based analysis (FBA) is a novel method to investigate the contribution of individual crossing fibers to the white matter damage and to detect possible alterations in both fiber density and fiber-bundle morphology. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS), on the other hand, quantifies the motion of brain metabolites in vivo, thus enabling the investigation of microstructural alteration of specific cell populations. The aim of this study was to identify novel specific microstructural imaging markers of white matter degeneration in HD, by combining FBA and DW-MRS. Twenty patients at an early stage of HD and 20 healthy controls were recruited in a monocentric study. Using diffusion imaging we observed alterations to the brain microstructure and their morphology in patients with HD. Furthermore, FBA revealed specific fiber populations that were affected by the disease. Moreover, the mean diffusivity of the intra-axonal metabolite N-acetylaspartate, co-measured with N-acetylaspartylglutamate (tNAA), was significantly reduced in the corpus callosum of patients compared to controls. FBA and DW-MRS of tNAA provided more specific information about the biological mechanisms underlying HD and showed promise for early investigation of white matter degeneration in HD.
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Project description:Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are characterized by progressive white matter (WM) alterations associated with the prion-like spreading of four-repeat tau, which has been pathologically confirmed. It has been challenging to monitor the WM degeneration patterns underlying the clinical deficits in vivo. Here, a fiber-specific fiber density and fiber cross-section, and their combined measure estimated using fixel-based analysis (FBA), were cross-sectionally and longitudinally assessed in PSP (n = 20), CBS (n = 17), and healthy controls (n = 20). FBA indicated disease-specific progression patterns of fiber density loss and subsequent bundle atrophy consistent with the tau propagation patterns previously suggested in a histopathological study. This consistency suggests the new insight that FBA can monitor the progressive tau-related WM changes in vivo. Furthermore, fixel-wise metrics indicated strong correlations with motor and cognitive dysfunction and the classifiability of highly overlapping diseases. Our findings might also provide a tool to monitor clinical decline and classify both diseases.
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Project description:Cerebral small vessel disease (CSVD) is a common cause of morbidity and cognitive decline in the elderly population. However, characterizing the disease pathophysiology and its association with potential clinical sequelae in early stages is less well explored. We applied fixel-based analysis (FBA), a novel framework of investigating microstructural white matter integrity by diffusion-weighted imaging, to data of 921 participants of the Hamburg City Health Study, comprising middle-aged individuals with increased cerebrovascular risk in early stages of CSVD. In individuals in the highest quartile of white matter hyperintensity loads (n = 232, median age 63 years; IQR 15.3 years), FBA detected significantly reduced axonal density and increased atrophy of transcallosal fiber tracts, the bilateral superior longitudinal fasciculus, and corticospinal tracts compared to participants in the lowest quartile of white matter hyperintensities (n = 228, mean age 55 years; IQR 10 years). Analysis of all participants (N = 921) demonstrated a significant association between reduced fiber density and worse executive functions operationalized by the Trail Making Test. Findings were confirmed by complementary analysis of diffusion tensor metrics.
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Project description:Magnetic resonance imaging studies typically use standard anatomical atlases for identification and analyses of (patho-)physiological effects on specific brain areas; these atlases often fail to incorporate neuroanatomical alterations that may occur with both age and disease. The present study utilizes Parkinson's disease and age-specific anatomical atlases of the subthalamic nucleus for diffusion tractography, assessing tracts that run between the subthalamic nucleus and a-priori defined cortical areas known to be affected by Parkinson's disease. The results show that the strength of white matter fiber tracts appear to remain structurally unaffected by disease. Contrary to that, Fractional Anisotropy values were shown to decrease in Parkinson's disease patients for connections between the subthalamic nucleus and the pars opercularis of the inferior frontal gyrus, anterior cingulate cortex, the dorsolateral prefrontal cortex and the pre-supplementary motor, collectively involved in preparatory motor control, decision making and task monitoring. While the biological underpinnings of fractional anisotropy alterations remain elusive, they may nonetheless be used as an index of Parkinson's disease. Moreover, we find that failing to account for structural changes occurring in the subthalamic nucleus with age and disease reduce the accuracy and influence the results of tractography, highlighting the importance of using appropriate atlases for tractography.
| S-EPMC6699705 | biostudies-literature
Project description:BackgroundThe underlying white matter impairment in patients with early and late-onset Alzheimer's disease (EOAD and LOAD) is still unclear, and this might due to the complex AD pathology.MethodsWe included 31 EOAD, 45 LOAD, and 64 younger, 46 elder controls in our study to undergo MRI examinations. Fiber density (FD) and fiber bundle cross-section (FC) were measured using fixel-based analysis based on diffusion weighted images. On whole brain and tract-based level, we compared these parameters among different groups (p<0.05, FWE corrected). Moreover, we verified our results in another independent dataset using the same analyses.ResultsCompared to young healthy controls, EOAD had significantly lower FD in the splenium of corpus callosum, limbic tracts, cingulum bundles, and posterior thalamic radiation, and higher FC in the splenium of corpus callosum, dorsal cingulum and posterior thalamic radiation. On the other hand, LOAD had lower FD and FC as well. Importantly, a similar pattern was found in the independent validation dataset. Among all groups, both the FD and FC were associated with cognitive function. Furthermore, FD of fornix column and body, and FC of ventral cingulum were associated with composite amyloid and tau level (r=-0.34 and -0.53, p<0.001) respectively.ConclusionsEOAD and LOAD were characterized by distinct white matter impairment patterns, which may be attributable to their different neuropathologies.
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Project description:Tremor is one of the most visible features of Parkinson's disease (PD), and the majority of PD patients experience tremor during the course of the disease. However, the distress caused by this cardinal motor feature for patients early in the course of their PD is commonly underappreciated. People living with early stage PD often experience intense embarrassment and difficulties due to their tremor that limit social interactions, and tremor frequently interferes with the ability to perform activities of daily living and simple tasks at home and work. Although tremor is primarily managed with medications, both tremor response and satisfaction with medical therapy are highly variable. This review offers an overview of reports of the patient experience of tremor in early stage PD and current management options for this cardinal motor feature.
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Project description:IntroductionWhile progressive MRI brain changes characterize advanced Parkinson's disease (PD), little has been discovered about structural alterations in the earliest phase of the disease, i.e. in patients with motor symptoms and with normal cognition. Our study aimed to detect grey matter (GM) and white matter (WM) changes in PD patients without cognitive impairment.MethodsTwenty PD patients and twenty-one healthy controls (HC) were tested for attention, executive function, working memory, and visuospatial and language domains. High-resolution T1-weighted and 60 directional diffusion-weighted 3T MRI images were acquired. The cortical, deep GM and WM volumes and density, as well as the diffusion properties of WM, were calculated. Analyses were repeated on data flipped to the side of the disease origin.ResultsPD patients did not show any significant differences from HC in cognitive functioning or in brain volumes. Decreased GM intensity was found in the left superior parietal lobe in the right (p<0.02) and left (p<0.01) flipped data. The analysis of original, un-flipped data demonstrated elevated axial diffusivity (p<0.01) in the superior and anterior corona radiata, internal capsule, and external capsule in the left hemisphere of PD relative to HC, while higher mean and radial diffusivity were discovered in the right (p<0.02 and p<0.03, respectively) and left (p<0.02 and p<0.02, respectively) in the fronto-temporal WM utilizing flipped data.ConclusionsPD patients without cognitive impairment and GM atrophy demonstrated widespread alterations of WM microstructure. Thus, WM impairment in PD might be a sensitive sign preceding the neuronal loss in associated GM regions.
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Project description:White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease. Here, we assessed mean diffusivity alterations in the white matter in 64 mutation carriers compared to 45 non-carrier family non-carriers. Using tract-based spatial statistics, we mapped the interaction of mutation status by estimated years from symptom onset on mean diffusivity. For major atlas-derived fibre tracts, we determined the earliest time point at which abnormal mean diffusivity changes in the mutation carriers were detectable. Lastly, we assessed the association between mean diffusivity and cerebrospinal fluid biomarkers of amyloid, tau, phosphorylated-tau, and soluble TREM2, i.e. a marker of microglia activity. Results showed a significant interaction of mutations status by estimated years from symptom onset, i.e. a stronger increase of mean diffusivity, within the posterior parietal and medial frontal white matter in mutation carriers compared with non-carriers. The earliest increase of mean diffusivity was observed in the forceps major, forceps minor and long projecting fibres-many connecting default mode network regions-between 5 to 10 years before estimated symptom onset. Higher mean diffusivity in fibre tracts was associated with lower grey matter volume in the tracts' projection zones. Global mean diffusivity was correlated with lower cerebrospinal fluid levels of amyloid-β1-42 but higher levels of tau, phosphorylated-tau and soluble TREM2. Together, these results suggest that regionally selective white matter degeneration occurs years before the estimated symptom onset. Such white matter alterations are associated with primary Alzheimer's disease pathology and microglia activity in the brain.
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Project description:Age-related white matter degeneration is characterized by myelin breakdown and neuronal fiber loss that preferentially occur in regions that myelinate later in development. Conventional diffusion MRI (dMRI) has demonstrated age-related increases in diffusivity but provide limited information regarding the tissue-specific changes driving these effects. A recently developed dMRI biophysical modeling technique, Fiber Ball White Matter (FBWM) modeling, offers enhanced biological interpretability by estimating microstructural properties specific to the intra-axonal and extra-axonal spaces. We used FBWM to illustrate the biological mechanisms underlying changes throughout white matter in healthy aging using data from 63 cognitively unimpaired adults ages 45-85 with no radiological evidence of neurodegeneration or incipient Alzheimer's disease. Conventional dMRI and FBWM metrics were computed for two late-myelinating (genu of the corpus callosum and association tracts) and two early-myelinating regions (splenium of the corpus callosum and projection tracts). We examined the associations between age and these metrics in each region and tested whether age was differentially associated with these metrics in late- vs. early-myelinating regions. We found that conventional metrics replicated patterns of age-related increases in diffusivity in late-myelinating regions. FBWM additionally revealed specific intra- and extra-axonal changes suggestive of myelin breakdown and preferential loss of smaller-diameter axons, yielding in vivo corroboration of findings from histopathological studies of aged brains. These results demonstrate that advanced biophysical modeling approaches, such as FBWM, offer novel information about the microstructure-specific alterations contributing to white matter changes in healthy aging. These tools hold promise as sensitive indicators of early pathological changes related to neurodegenerative disease.
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